The objective of this proposal is to develop and characterize in vitro models of human cell-mediated immune responses to hapten-conjugated cells. Both primary and secondary immune responses will be investigated, utilizing proliferative and cytotoxic assays of immunological function. Most experiments will utilize trinitrophenyl-conjugated cells, however dinitrophenyl and fluorescein conjugates will also be studied. The role of major histocompatibility complex gene products in such responses will be of particular interest in two respects. First, we will investigate the possible role of HLA-associated Ir genes as determinants of responsiveness to hapten-conjugated cells. These studies will be performed in families, in an effort to associate high or low responsiveness with the inheritance of the HLA complex. Second, we will characterize the role of HLA-antigens in induction and elicitation of responses to hapten-conjugated cells. Finally, we will examine the role of monocytes/macrophages and various lymphocyte subpopulations in the generation and regulation of such responses.